Variability in morphology and immunohistochemistry of Crohn's disease-associated small bowel neoplasms: implications of Claudin 18 and Cadherin 17 expression for tumor-targeted immunotherapies.

AIMS: Inflammatory bowel disease-associated colorectal carcinomas are known to have different morphology, immunoprofile, and genetic findings from sporadic colorectal carcinomas; however, little is known for Crohn's disease-associated small bowel neoplasms (CD-SBNs). Cadherin 17 is a useful biomarker of adenocarcinomas with intestinal phenotype and recently reported as an ideal target for chimeric antigen receptor T-cells (CAR-T) therapy for gastrointestinal carcinoma. Claudin 18 is a cell adhesion protein, and Claudin18 isoform 2 (CLDN18.2) is frequently expressed at high levels in gastric-type adenocarcinoma. Zolbetuximab, a targeted monoclonal antibody, has been developed for CLDN18.2-positive gastroesophageal adenocarcinoma. We examined a series of CD-SBNs for both Cadherin 17 and Claudin 18, and also hypothesized that expression of Claudin 18 was associated with gastric phenotype. METHODS AND RESULTS: We performed histological and immunohistochemical examinations on 25 CD-SBNs. Most of adenocarcinomas showed tubular morphology as seen in gastric carcinomas, whereas a subset of dysplasia was morphologically similar to that of the large bowel. Cadherin17 and Claudin 18 expression was identified in 93% and 57% CD-associated adenocarcinomas respectively. In Cadherin 17-positive CD-SBNs, frequent MUC5AC, MUC6, and Claudin18 expression was identified (61%, 57%, and 57%, respectively). Claudin 18-positive CD-SBNs showed significantly more MUC5AC and MUC6 expression than Claudin 18-negative CD-SBNs (P = 0.005, < 0.001 respectively). CONCLUSION: In CD-associated small bowel adenocarcinomas, Cadherin 17 expression was frequently retained and Claudin 18 was frequently co-expressed. Claudin 18 had a positive correlation with the expression of gastric mucins. These results suggest that CD-associated small bowel adenocarcinomas may be candidates for Cadherin 17- and Claudin 18-targeted immunotherapies.

Evaluation of the Safety and Efficacy of Modified Laparoscopic Suture Rectopexy for Rectal Prolapse.

Objectives: There are many surgical options for the treatment of rectal prolapse. To date, the efficacy of mesh-free laparoscopic suture rectopexy remains unclear due to the limited number of reports. This study aimed to evaluate the safety and efficacy of laparoscopic suture rectopexy. Methods: This observational cohort study is a retrospective cross-sectional analysis of a continuously maintained database. All patients underwent laparoscopic suture rectopexy for rectal prolapse between April 2012 and March 2018. The primary outcomes measured were recurrence rates and complications of laparoscopic suture rectopexy. Results: A total of 268 patients (29 male and 239 female) underwent laparoscopic suture rectopexy. Their mean age was 77 (19-95) years, and the mean prolapse length was 6.4 (3.5-20) cm. One patient suffered an intraabdominal abscess. Spondylitis developed in another patient following surgery. The median follow-up period was 45 (12-82) months. A total of 22 patients (8.2%) developed recurrence. The average time to recurrence was 15.6 (1-44) months. Multivariate analysis revealed a significant correlation between recurrence and prolapse length >7.0 cm (OR: 1.26, 95% CI: 1.38-1.42, P < 0.01). Conclusions: Laparoscopic suture rectopexy for complete rectal prolapse is a minimally invasive and safe procedure that may lead to lower recurrence rates.

Longer prolapsed rectum length increases recurrence risk after Delorme's procedure.

PURPOSE: Risk factors for recurrence of rectal prolapse after surgery remain unclear. Delorme's procedure is often selected for relatively small-sized rectal prolapse, but there are few reports discussing the association between prolapsed rectum length and prolapse recurrence after Delorme's procedure. We hypothesized that patients with longer rectal prolapses are at a higher risk of recurrence after Delorme's procedure. METHODS: The study population comprised patients with rectal prolapse who underwent Delorme's procedure between January 2014 and December 2019 at Tokyo Yamate Medical Center. We extracted data on patient age, sex, body mass index, previous history of anal surgery, previous history of surgery for rectal prolapse, and length of prolapse, to identify risk factors for prolapse recurrence. RESULTS: Altogether, 96 patients were eligible for analysis. The median length of the prolapsed rectum was 3.0 cm (range, 1.0-6.6 cm). Twenty-four patients (25.0%) experienced recurrence after Delorme's procedure after a median of 7.5 months (interquartile range, 3.2-20.9 months). Multivariate analysis revealed that longer prolapsed rectum length increased the risk of recurrence after Delorme's procedure (hazard ratio, 6.28; 95% confidence interval, 1.83-21.50; P<0.001). CONCLUSION: The length of the prolapsed rectum should be measured before Delorme's procedure for rectal prolapse, because length is associated with a risk of recurrence after the surgery.